To circumvent the major threats of low blood volume and low blood pressure, animals need powerful mechanisms for salt and water conservation, which is renin–angiotensin system (RAS). Activation of the RAS is, therefore, a useful response in many demanding situations. However, increased activity of the RAS, especially in combination with other cardiovascular risk factors, may lead to a cascade of deleterious effects such as hypertension, atherosclerosis, myocardial remodeling, heart failure, ischemic stroke, and diabetes mellitus. Although many pathophysiological actions of angiotensin (Ang) II may still be viewed as being homeostatic in principle, its over-activation can be detrimental.. Numerous experimental studies have indicated that angiotensin-converting enzyme (ACE) 2 efficiently hydrolyzes the potent vasoconstrictor Ang II to Ang 1–7. Thus, the axis formed by ACE 2/Ang 1–7/Mas appears to represent an endogenous counterregulatory pathway within the RAS, the actions of which are in opposition to the vasoconstrictor/proliferative arm of the RAS consisting of ACE, Ang II, and AT1 receptor. Although most of the well-known cardiovascular and renal effects of RAS are attributed to ACE, an important enzyme in the generation of Ang II, much less is known about the function of ACE 2. This review summarizes the recently published data on basic properties of ACE 2 and Ang 1–7 and the evidence from experimental and clinical studies of various pathological conditions related to the biological roles of ACE 2/Ang 1–7/Mas in the heart.